The entry of an enveloped virus into a target cell is initiated by the envelope protein of the virus binding to a receptor on the target cell membrane. The interaction of the receptor and the viral envelope protein triggers fusion between the envelope protein and the target cell membrane, permitting the entry of the viral genome into the cytoplasm of the target cell. The fusion mediated by the viral envelope protein also permits cell-to-cell transmission of enveloped viruses. The expression of the viral envelope protein on the membrane of an infected cell can trigger fusion with an uninfected cell bearing the appropriate viral envelope protein receptor, further increasing the virulence of the virus within the host. Thus, the receptor-viral envelope protein determines the tropism, virulence, and ultimately the pathogenicity of the virus in a particular host.
In HIV the viral envelope protein requires both a receptor and a co-receptor for the initiation of fusion events. The entry of HIV into target cells is mediated by a fusion reaction in which the gp120/gp41 glycoprotein of the virus binds to CD4 and a CC chemokine receptor, CCR5 or CXCR4, on the target cell membrane. The HIV enveloped surface glycoproteins are synthesized as a single 160 kD precursor protein which is cleaved by a cellular protease during viral budding into two glycoproteins, gp41 and gp120. gp41 is a transmembrane protein and gp120 is an extracellular protein which remains non-covalently associated with gp41, possibly in a trimeric or multimneic form.
The tropism and virulence of HIV appears to be determined by the co-receptor used to bind the viral envelope protein. HIV strains using the CCR5 as a co-receptor mediate transmission and predominate early in the course of disease, while those using CXCR4 are mainly associated with the symptomatic phase emerging in later disease stages and have been linked to a more rapid CD4+ T-cell depletion and progression to AIDS. Therefore, there remains a need for assays able to determine HIV-1 co-receptor usage, or tropism, that are quick, accurate and have the sensitivity required to detect minor non-R5 chemokine receptor variants.